Our long term goal is to improve glycemic control in adolescents with Type 1 diabetes mellitus (T1DM) through the use of oral hypoglycemic agents as adjuncts to insulin therapy. In T1DM pubertal development is associated with increased insulin resistance and worsening glycemic control. Metabolic abnormalities such as postprandial hyperglycemia and hyperglucagonemia are known to contribute to poor glycemic control in T1DM. The biguanide metformin can improve insulin resistance and decrease insulin requirements in patients with T1DM. Sitagliptin is an oral hypoglycemic agent that acts as an incretin enhancer by increasing the circulation of endogenous active GLP-1. The incretin GLP-1 lowers postprandial hyperglycemia by stimulating of endogenous insulin secretion and suppressing glucagon. We propose to examine the glucose lowering effect of metformin and sitagliptin as adjuvants to standard insulin therapy in adolescents with T1DM. We hypothesize that in adolescents with T1DM, the combined use of metformin and sitagliptin as adjuvants to standard insulin therapy will lower postprandial hyperglycemia more than insulin or the addition of each agent alone. To understand the glucose lowering effect of these agents and their combination with insulin we will examine the mechanisms by which these drugs lower glycemia. By targeting multiple metabolic abnormalities with oral hypoglycemic agents we might be able to improve glycemic control in adolescents with T1DM.